This research project encompasses a number of different approaches to both understand how current antitubercular chemotherapy works using the most modern technologies and to use this information to develop new and improved therapies and therapeutic approaches. Individual projects within this framework are aimed at; (1) understanding the biochemical mode of action of existing front-line antituberculars such as isoniazid, pyrazinamide and ethambutol, (2) understanding the action of various agents in animal models of tuberculosis therapy, and (3) understanding the development of resistance within patients undergoing chemotherapy. The project relies on the development of advanced animal models for predicting drug efficacy under real world conditions. In addition, development of screening assays that would predict drugs able to shorten the current duration of therapy or treat latent infections have been a large focus. Section scientists continue to be involved in elucidating the mechanism of action of various antibiotics, such as pyrazinamide, or the nitroimidazopyrans, the only new class of antibiotics advanced for preclinical consideration since rifampicin. Section scientists have also been involved in understanding the mechanism of action of second-line antituberculars and the evolution of multidrug resistance in patients in South Korea and Cambodia.